Aloe vera gel for prevention of chemotherapy-induced hyperpigmentation: Four case reports

Rationale: This study aimed to evaluate the efficacy of topical application of Aloe vera gel in preventing chemotherapy-induced hyperpigmentation (CIH). CIH is a common side effect of chemotherapy that causes skin irritation, redness, and itching. Aloe vera has been studied for its potential use in treating radiation-induced dermatitis, which may help alleviate some of the symptoms associated with this condition. Patient concerns: In this study, 4 children requiring curative chemotherapy were prospectively enrolled and treated with Aloe vera gel. Diagnosis: Acute skin reactions were monitored and classified according to the Common Terminology Criteria for Adverse Events Grading Scale. Interventions: Patients were asked to use the gel on one-half of the body field twice daily from the beginning of treatment until 4 weeks after the completion of chemotherapy, with no medication to be used on the other half. Outcomes: The results indicate that applying Aloe vera gel may reduce the visibility of hyperpigmentation at subsequent time points. The most important observation was that the continued application of Aloe vera gel 4 weeks after the completion of chemotherapy was effective in reducing the grading of CIH. Lessons: These effects highlight the potential of Aloe vera gel as a topical onconutraceutical treatment for CIH.


Introduction
Dermatologic adverse reactions to anticancer therapies can negatively influence dosing and quality of life (QOL). The type and severity of skin reactions can vary depending on the chemotherapy drugs used, dosage, and sensitivity of the individual to these drugs.
Aloe vera is a juicy plant species belonging to the genus Aloe. It has anti-inflammatory and moisturizing properties, which can help soothe and hydrate the skin. It can also help to reduce redness and irritation. Some studies have found that the topical application of aloe vera gel to the affected area can help reduce the severity of radiation-induced dermatitis. [1][2][3] Aloe vera is a herbal remedy with an established history of use. It has also been reported to exert a protective effects against radiation-induced skin damage. [4] Aloe vera gel has an extensive range of biological activities, including antifungal, anti-inflammatory, and hepatoprotective properties. [5] Evaluation of Aloe vera in a randomized trial against the best clinical practice or placebo would have non-removable ambiguities because the best clinical practice is unknown or mostly agreed on and because even a placebo may also affect radiation skin reactions through its moisturizing or other properties. [1] Considering the aforementioned factors and uncertainties regarding using Aloe vera to prevent chemotherapy-induced hyperpigmentation (CIH), we decided to examine this issue in a self-controlled clinical trial.

2.1.Data source
Accurate diagnosis and appropriate management of chemotherapy-related adverse effects requires clinicians to know the most common skin reaction patterns for the drugs that patients receive. All study procedures were conducted at the Chang Gung Memorial Hospital. Informed consent was obtained before inclusion of the patients. Requests for approval to access groups under 18 years of age were assessed on a case-by-case basis by the Institutional Review Board (IRB). Patients must be conscious, awake, and able to understand and answer fluent Chinese questions in Chinese.
For the intervention, a commercially available Aloe vera gel was provided to patients with CIH, who were asked to use the gel on only one half of the body field twice daily from the beginning of treatment until four weeks after completion of chemotherapy, with no medication to be used on the other half. The gel provided to the patients included Aloe vera in addition to lanolin oil, glyceryl stearate, diluted collagen, tocopherol, allantoin, and paraben. In the case of symptomatic CIH, TC treatment routine of topical corticosteroids was prohibited over the entire treatment area. The dorsal and palmar surfaces of one hand were applied, whereas the other hand served as thea control.
The aim of using Aloe vera gel to prevent CIH is to reduce the severity and duration of skin reactions caused by cancer treatment, improve patients' QOL, and minimize the need for additional medications to manage skin-related side effects.

Trial oversight
The trial was approved by the Eethics Ccommittee of Chang Gung Memorial Hospital and followed the Good Clinical Practice guidelines of the International Council for Harmonization and the provisions of the Declaration of Helsinki. All parents or guardians of the patients provided written informed consent. In compliance with the regulations of the IRB (202100082A3), we prospectively analyzed the data.

Results
Although research has not been extensive, there are encouraging signs that they can effectively fade post-chemotherapy hyperpigmentation (Figure 1). The half applied with Aloe vera gel showed reduced grade severity of hyperpigmentation compared to the other half that had not been applied (Figure 2). It should be noted that hyperpigmentation can be induced by some chemotherapy agents. Therefore, the tumor may not disappear if the patient continues to receive chemotherapy.
Although Aloe vera is commonly used to treatfor various skin conditions, there is limited scientific evidence to support its use, specifically for the prevention of CIH. Aloe vera is supposed to work by moisturizing and cooling the skin, reducing inflammation, and promoting the growth of new skin cells. At the end of the study, theour patients were satisfied with their skincaring outcomes.

Discussion
However, classicside chemotherapyeffects isare often associatedencountered with adverseclassic effectschemotherapy. The most common side effect iwas dermatological. [6] Some chemotherapy agents, including ifosfamide, cyclophosphamide, daunorubicin, bleomycin, busulfan, 5-fluorouracil, platinum-based agents, and thiotepa, can cause and exacerbate hyperpigmentation, which can impair QOL. [7,8] It can be localized, diffuse, or have a distinctive pattern. [9,10] Phytochemicals are natural compounds extracted or derived from plants, and have been reported for skin hyperpigmentation treatment owing to various mechanisms that inhibit melanogenesis. Aloesin, a glycoprotein extracted from Aloe vera, was reported to exhibit antityrosinase activity in a dose-dependent manner. It works by inhibiting L-DOPA oxidation and has shown better affinity than kojic acid, arbutin, etc. [11] Aloe Vera has been used to treat eczema, skin burn, frostbite, and other dermatologic diseases for many years. [12] While there is little scientific evidence that Aloe vera can reduce the size of hyperpigmented spots, some studies have reported that it works to lighten dark spots. [13] Post-chemotherapy hyperpigmentation can be a temporary or long-term side effect of chemotherapy, depending on the individual and the drugs used for treatment. [14] In most cases, hyperpigmentation fades over time; however, it can take several months or even years for the skin to return to its normal color. However, this study examined an alternative option to solve the problem of hyperpigmentation affecting the QOL.

Conclusion
While Aloe vera gel may benefit the skin, more research is needed to determine its effectiveness in treating CIH. Although there are various indications for its use, randomized controlled trials are the best method forto determininge its efficacy.